The endocrine system is critical to cell-cell communication. In the endocrine system, hormones are secreted by endocrine glands into the circulatory system and adsorbed onto specific receptors, usually located distal to the site of secretion. The endocrine system is used to orchestrate a variety of different physiological processes, including metabolism, growth and maturation, circadian cycles and the like. An important member of the endocrine system is the hypothalamic-pituitary axis. Principal neuropeptides secreted by the hypothalamus include growth hormone releasing hormone (GHRH), growth hormone release-inhibiting hormone (somatostatin), prolactin release inhibitory factor (dopamine), gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), and thyrotropin-releasing hormone (TRH). Hormones released by the pituitary in response to hypothalamus neuropeptide influence include growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH, corticotropin) and thyrotropin (thyroid stimulating hormone, TSH). Growth hormone (GH) is a peptide present in plasma. It is a 191 amino acid peptide secreted into the blood stream. Growth hormone acts on receptors in the liver, muscle, fat, growth plate and in other tissues. Its actions on skeletal growth and on protein anabolism are mediated at least in large part by insulin-like growth factor-1 (IGF-1) which is a peptide present in plasma and other body fluids. It comprises 70 amino acids, including 3 disulphide bonds, and can stimulate growth of a wide range of cell types and it mediates the effects of growth hormone on skeletal growth. Human IGF-I has been purified from plasma and its complete amino acid sequence is established. IGF-1 is released by the liver into the blood stream in response to stimulation by GH. Growth hormone is also produced in tissues including muscle in response to the action of GH. Human GH has been purified from human tissues and the complete amino acid sequences established. GH is found in other species including ruminants with extensive homologies to those in humans. Growth hormone (GH) or somatotropin, secreted by the pituitary gland constitute a family of hormones which biological activity is fundamental for the linear growth of a young organism but also for the maintenance of the integrity at its adult state.
Growth hormone is released from the pituitary. The release is under tight control of a number of hormones and neurotransmitters either directly or indirectly. The control of growth hormone production and secretion is complex, but is mainly under the influence of growth hormone releasing hormone (GHRH) and somatostatin, which stimulate and inhibit it, respectively. Secretion of GH is stimulated by the GHRH, and inhibited by somatostatin, and both are hypothalamic hormones. The shifting balance between these regulatory agents is responsible for the pulsatile nature of GH secretion. GH pulses are a result of GHRH secretion that is associated with a diminution or withdrawal of somatostatin secretion. In addition, the pulse generator mechanism is timed by GH-negative feedback. The endogenous rhythm of growth hormone secretion becomes entrained to the imposed rhythm of exogenous GH administration. Effective and regulated expression of the GH and IGF-I pathway is essential for optimal linear growth, homeostasis of carbohydrate, protein, and fat metabolism, and for providing a positive nitrogen balance. Growth hormone release can be stimulated by growth hormone releasing hormone (GHRH) and inhibited by somatostatin. In both cases the hormones are released from the hypothalamus but their action is mediated primarily via specific receptors located in the pituitary. Growth hormone releasing hormone (GHRH), also known as growth hormone releasing factor, is a hypothalamic peptide which positively regulates the synthesis and secretion of growth hormone in the anterior pituitary. In addition to the two primary endogenous regulators of GH release, hypothalamic hormone somatostatin (SS) and stimulated by GH-releasing hormone (GHRH), a number of other peptidyl/nonpeptidyl compounds have been shown to stimulate GH release primarily through the pituitary-hypothalamus axis. These include the peptides galanin, pituitary adenylate cyclase-activation peptide (PACAP), delta sleep-inducing peptide (DSIP), and angiotensin II. Glucocorticoids and thyroid hormones, and various carbohydrates, amino acids, fatty acids and other biomolecules, are also known to directly or indirectly regulate GH secretion. The growth hormone production pathway is composed of a series of interdependent genes whose products are required for normal growth. Effective and regulated expression of the GH pathway is essential for optimal linear growth, as well as homeostasis of carbohydrate, protein, and fat metabolism. Most GH is secreted at night, during deep sleep, but some is secreted in response to exercise and other forms of physical stress. Growth hormone secretion rates are highest in adolescents and lowest in the elderly.
Growth hormone (GH) is an essential regulator of carbohydrate and lipid metabolism, participating in glucose uptake and usage, accelerating fat expenditure, preventing triglyceride accumulation, and facilitating lipid mobilization in adipose tissues. GH has a common range of actions including somatic growth, differentiation and intermediary metabolism, effects that are mediated by GH-induced insulin-like growth factor-1. Growth factors are polypeptides which stimulate a wide variety of biological responses (e.g. DNA synthesis, cell division, expression of specific genes, etc.) in a defined population of target cells. A variety of growth factors have been identified, including the transforming growth factor beta family, epidermal growth factor and transforming growth factor alpha (the TGF-.alpha.s), the platelet-derived growth factors (PDGFs), the fibroblast growth factor family (FGFs) and the insulin-like growth factor family (IGFs), which includes IGF-I and IGF-II. IGF-I and IGF-II are related in amino acid sequence and structure, with each polypeptide having a molecular weight of approximately 7.5 kilodaltons (kDa). IGF-I mediates the major effects of growth hormone, and is thus the primary mediator of growth after birth. IGF-I has also been implicated in the actions of various other growth factors, since the treatment of cells with such growth factors leads to increased production of IGF-I. IGF-1 is the major regulator of post-natal growth, and has both endocrine and paracrine action on different tissues. GH acts directly or indirectly on the peripheral organs by stimulating the synthesis of growth factors (IGF-I) or of their receptors (epidermal growth factor or EGF). IGF-I and GH, in turn, feedback on the hypothalamus and pituitary to inhibit GHRH and GH release. GH elicits both direct and indirect actions on peripheral tissues, the indirect effects being mediated mainly by IGF-I. The direct action of GH is of the type referred to as anti-insulinic, which favors the lipolysis at the level of adipose tissues. Through its action on IGF-I synthesis and secretion, GH stimulates the growth of the cartilage and the bones (structural growth), the protein synthesis and the cellular proliferation in multiple peripheral organs, including muscles and the skin. Through its biological activity, growth hormone participates within adults at the maintenance of a protein anabolism state, and plays a primary role in the tissue regeneration phenomenon after a trauma. Growth hormone is a hormone which stimulates growth of all tissues capable of growing. Growth hormone, well recognized as a general anabolic agent, promotes a myriad of physiological effects throughout the life-cycle. It is a growth promoter responsible for skeletal growth and a potentiator of protein synthesis. Growth hormone also displays insulin-potentiating properties, has weak lactogenic activity and plays a role in lipid metabolism and homeostatic maintenance. Growth hormone (GH) has pleiotropic effects on cholesterol metabolism. GH stimulates the expression of hepatic low density lipoprotein (LDL)-receptors and the activity of cholesterol 7-alpha-hydroxylase, a key regulatory step in bile acid synthesis. In addition, growth hormone is known to have a number of effects on metabolic processes, e.g., stimulation of protein synthesis and free fatty acid mobilisation and to cause a switch in energy metabolism from carbohydrate to fatty acid metabolism. Deficiency in growth hormone can result in a number of severe medical disorders, e.g., dwarfism.
Reduced growth hormone secretion from the anterior pituitary causes skeletal muscle mass to be lost during aging from 25 years to senescence. The growth hormone deficiency could be the result of an aberration directly affecting a growth hormone pathway, indirectly affecting a growth hormone pathway, or not affecting a growth hormone pathway at all. The principal feature of GH deficiencies in children is short stature. The huamn growth hormone for GH deficiency treatment can be a naturally occurring growth hormone, for example isolated from animal tissues or a body fluid, or can be a synthetic equivalent of a naturally occurring growth hormone, for example a growth hormone produced by recombinant DNA techniques. Nowadays large scale production for both hormones is readily achieved using recombinant DNA techniques. Recombinant HGH has been used successfully in the treatment of pituitary dwarfism; it removes fatty acids and is therefore used in the treatment of obesity, it improves vascularization and promotes muscle mass gain in the elderly,; it is used in the treatment of ulcers and bone fractures and accelerate the regeneration of damaged tissues. HGH treatment in growth hormone deficient patients results in the stimulation of skeletal growth, an increase in cellular protein synthesis, an increase in serum glucose and insulin levels, a reduction in body fat stores, and stimulation of connective tissue and mineral metabolism. The elevation of growth hormone levels can also be accomplished by application of growth hormone releasing peptides (GHRPs). However, HGH has serious known risks. Among the possible long-term side effects of HGH is an increased risk of cancer, and other dangerous side effects include nerve pain and elevated cholesterol and glucose levels. Chronic elevation of growth hormone levels in humans usually results in either gigantism or acromegaly. It has been reported that recombinant GH stimulates skeletal growth in GH deficiency and that it reduces protein catabolism in patients with severe catabolic illness consequence on surgery or burns. |
|
